Perfecting Pitch

Perfecting Pitch

For about 60 years, inner-ear studies have focused on the sensory cells and their interaction with the basilar membrane, a group of thin elastic fibers. When a sound enters the ear, it causes the basilar membrane to move up and down, propagating a wave. The wave travels quickly along the membrane and down the ­spiral-­shaped portion of the inner ear known as the cochlea, which is tuned to different frequencies along its length. When a wave reaches the part of the cochlea tuned to its frequency, it slows down. And as waves travel, they stimulate the hair cells located above the basilar membrane, which convert the waves into nerve impulses and also vibrate in a way that amplifies the wave motion.

Individual sensory cells can’t produce cochlear amplification by themselves. To figure out how they collaborate, Freeman’s team looked to the tectorial membrane, which lies above the hair cells and in which they’re embedded.

But the tectorial membrane isn’t easy to study. “It’s like a slab of Jell-O,” says Alexander Aranyosi, PhD ‘02, a research scientist who worked on the study. Roughly two centimeters long, less than half a millimeter wide, and thinner than a human hair, the membrane is hard to manipulate–and nearly transparent. If exposed to air, it shrivels up, since it’s 97 percent water.

The contents of the remaining 3 percent, however, are intriguing. In addition to sugar, the membrane contains alpha-tectorin and beta-tectorin, two proteins found nowhere else; mammals lacking the genes that make them have congenital hearing impairments. So Freeman encouraged Ghaffari to think about how to simulate natural stimulation of the tectorial membrane in the lab.

Ghaffari suspended a half-millimeter piece of a mouse’s tectorial membrane across two tiny supports, each 300 micrometers thick, which he built on a glass slide and placed in a saline solution that simulates the cochlear environment. One support is glued to the slide; the other is attached to a piezoelectric actuator and loosely coupled to the slide. When an oscillating voltage is applied to the actuator, it vibrates at a corresponding audio frequency and moves the attached support, causing a wave to travel down the suspended membrane. Using a stroboscopic imaging system developed earlier in Freeman’s lab and built by Aranyosi, Ghaffari measured ­nanometer-­scale displacements of the membrane at up to several thousand cycles per second–frequencies perfect for hearing.

The team observed that waves move side to side along the tectorial membrane (waves traveling along the basilar membrane move up and down). The researchers also discovered that waves move along the tectorial membrane at about the same speed as basilar-membrane waves that have reached the part of the cochlea tuned to their frequency. “When you’ve got two waves moving at the same speed, that gives them the possibility to interact,” Aranyosi says. “They can trade energy back and forth.” The two kinds of waves travel at the same speed at only one spot–where the cochlea is tuned to a sound’s frequency. Here, the ear is able to selectively amplify, and thus distinguish, a specific frequency.

The group’s next step is to measure these interactions in vivo. “Once we have a better understanding of how those wave interactions take place, then we can build hearing aids that actually correct for the real problem rather than simply trying to make everything sound louder,” Aranyosi says. The researchers also plan to study the genes that produce the tectorial membrane’s two unique proteins for more clues about how cochlear amplification works.

In the nonhierarchical Freeman lab, discussion topics range from Eastern philosophies to new methodologies for probing the cochlea. “We all treat each other as colleagues and coworkers, as opposed to professor and student or research scientist and student,” Aranyosi says. “Everybody has something to contribute, and everyone is given an equal voice in how we do things.”

“A lot of subtle ideas come out of these meetings where we’re all just hanging out with Denny,” Ghaffari says. “That’s just the way Denny is.”